This shared resource provides fee-for-service support for many aspects of the generation and study of mouse models human cancer. The ES Cell and Transgenics Facility specializes in assisting researchers with the design, generation, maintenance, and analysis of mice containing designer mutations. The staff also provides skilled assistance with a variety of protocols utilizing mouse ES cells (establishment of new lines, differentiation into specific cell types). Members of the Koch Institute have been leaders in the use of mouse models to study the molecular basis of the tumor development and increasingly in cancer treatment and resistance. The ES Cell & Transgenics Core Facility (formerly the Transgenic Animal Core) acts as a centralized service to ensure that all Kl members have access to mouse modeling technology. Specifically, the Core provides consultative services to help Kl investigators design their gene targeting and overall modeling strategy, produces genetically-modified ES cells (by either gene targeting or de novo isolation from blastocytes) and conducts injections to generate chimeric and transgenic mice. The ES Cell &Transgenics Core places equal emphasis on investigator education and provides state-of-the-art training to Kl researchers in any or all the procedures required to create targeted ES cells, transgenics, and mutant mouse models. It also maintains a repository of useful mouse strains, including strains expressing Cre or Flp recombinase under tissue-specific or inducible promoters, which are provided on demand. Over the current funding period, there has been a dramatic increase in the number of Kl members who use this Core. To ensure that services are provided in a timely manner, the Core's ES Cell Suite has been relocated to an improved location and we have increased the staff, the T ES Cell &Transgenics Core has also continued to expand its services to remain on the cutting edge. For example, it has capitalized on its access to the scientists who first generated ES cell-derived mice by tetraploid embryo complementation by learning and optimizing this technique so that can be offered as a robust service. With an excellent menu of reliable and efficient services, flexibility to accommodate unique requests and a dedicated, talented and enthusiastic staff, the ES Cell &Transgenics Core is well situated to support Kl investigators in their goal of generating increasingly precise mouse models and also to continue to expand into new areas of cancer research using cutting-edge techniques.